Chlorzoxazone, 5-chlorobenzo[d]oxazol-2(3H)-one, is a muscle relaxant which acts at central level and is used in the treatment of muscle spasms and the resulting pain. Chlorzoxazone acts on the spinal cord, by depressing/suppressing the reflexes.
A number of examples of synthesis of chlorzoxazone (1) from 4-chloro-2-aminophenol, into which an acyl group, usually from urea or phosgene, is inserted, are described in the literature. Cases in which the carbonyl group inserted is directly gaseous CO are also reported.
A representative example of the use of urea for the synthesis of chlorzoxazone (1) is reported in U.S. Pat. No. 3,812,138 (DE2131366), which discloses the formation of dibenzothiazolones from various aminophenols/aminothiols in the presence of urea and mineral acids according to the following synthesis scheme:

Specifically, chlorzoxazone (1) is synthesised by loading concentrated HCl, 4-chloro-2-aminophenol and urea into an autoclave and heating them in an inert atmosphere at 125° C. After cooling to room temperature, the crystalline paste that precipitates is suspended in 1500 parts of water, the pH of the suspension is adjusted to 5-6, and the paste is heated at 100° C. for an hour. After cooling, the residue is filtered and washed under vacuum to obtain chlorzoxazone (1) with a yield of 91%.
The patent does not report the degree of purity of the product obtained and, despite the high yield of the process, this synthesis is not particularly economical in terms of energy because very high temperatures are used. Moreover, the required work-up considerably increases the volumes of work, making it inefficient on an industrial scale.
CN1560040 and CN103360336 also report the synthesis of chlorzoxazone (1) by reacting 4-chloro-2-aminophenol with urea at high temperatures in the presence of mineral acids (HCl or H2SO4).
CN1560040 also discloses the synthesis of chlorzoxazone using phosgene

The same document also describes the synthesis of chlorzoxazone (1) from the nitro derivative by reacting it with gaseous CO, which leads to the formation of cyclic carbamate

Another synthesis method involves cyclisation of 5-chloro-salicylamide by the action of 13% NaOH.

An alternative process using phosgene is reported in U.S. Pat. No. 3,369,022. The cyclisation of 4-chloro-2-aminophenol is described in procedure no. 2, according to the following synthesis scheme:

In particular, a solution of phosgene in ethyl acetate is dripped into a suspension of 4-chloro-2-aminophenol and sodium acetate in ethyl acetate. The reaction mixture is heated to reflux and cooled, then washed with water containing 5% hydrochloric acid. After a distillation under vacuum and a further crystallisation, the product is obtained.
The procedure does not provide any data relating to the yield or purity of the chlorzoxazone (1) obtained, but even if they were excellent, the process presents the significant drawback of the manageability of phosgene, a particularly reactive, toxic reagent which requires special precautions for both use and disposal.
Another example of synthesis of chlorzoxazone (1) involving the use of phosgene is reported in EP0477819. The procedure described therein also appears unsatisfactory in terms of yields.
Alternative methods of synthesising chlorzoxazone are described in U.S. Pat. No. 2,895,877. Starting with 2-amino-5-chlorobenzoxazole or N-(5-chloro-2-hydroxyphenyl)urea at reflux in 1N HCl a solid precipitates which, after a basic work-up and an acid work-up, is crystallised from a suitable solvent.
An alternative synthesis method not requiring the use of urea or phosgene is described in JP4834875, wherein a mixture of 4-chloro-2-nitrophenol, benzene, RhCl3 and V2O5 is heated in an autoclave with CO.

Also in JP58225072, chlorzoxazone (1) is obtained by heating a suitable nitrophenol with CO in hydrated organic solvent (e.g. THF) in the presence of a base (e.g. triethylamine) and selenium.
SK278412 describes a process wherein 4-chloro-2-nitrophenol is carbonylated with CO at high temperatures in the presence of catalytic systems such as S, COS, H2S or CS, bases (alkoxides, alkaline metal oxides, etc.) and vanadium derivatives (V2O5, V2S5, NH3VO3).
EP0087347 discloses (Example 7) the synthesis of chlorzoxazone (1) obtained directly from the nitro derivative in the presence of pyridine and of a catalyst based on palladium and molybdenum in a CO atmosphere (200 bars) at 200° C. Cyclic carbamate is then isolated by cooling, filtration of the catalyst and recrystallisation of the product from water.
The use of CO is problematic; said gas is highly poisonous, and insidious because it is odourless, colourless and tasteless. Its extremely hazardous nature requires particular precautions which make its industrial use extremely complicated.
RO75779 discloses the synthesis of chlorzoxazone (1) from 5-Cl-salicylamide; in particular, the desired product is obtained by treating the amide in water, NaOH and butanol with 13% NaOCl at 35° C.

On the basis of the information set out above, there is clearly a need to find a process for synthesising chlorzoxazone (1) that is easier to manage industrially, safer, by avoiding the use of reagents which are extremely hazardous to humans and the environment, and more economical.